TY - JOUR
T1 - Cellular and vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle
AU - García-Díaz, María
AU - Kawakubo, Masayoshi
AU - Mroz, Pawel
AU - Sagristà, M. Lluïsa
AU - Mora, Margarita
AU - Nonell, Santi
AU - Hamblin, Michael R.
N1 - Funding Information:
This work was supported by grants of the Spanish Ministry of Economy and Competitiveness ( CTQ2010-20870-C03 ) and US NIH ( RO1 AI050875 ) to MR Hamblin. M G-D thanks the Comissionat per a Universitats i Recerca del Departament d'Innovació, Universitats i Empresa de la Generalitat de Catalunya i del Fons Social Europeu for a predoctoral fellowship. The sponsors had no influence on the collection, analysis and interpretation of data; on the writing of the report; and on the decision to submit the article for publication. We thank Dr. David Sánchez-García for the synthesis of temocene and Dr. Salvador Borrós for the assistance with the Zetasizer Nano-ZS measurements.
PY - 2012/9/10
Y1 - 2012/9/10
N2 - The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG400/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene.
AB - The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG400/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene.
KW - Cellular targeting
KW - Drug delivery vehicle
KW - Photodynamic therapy
KW - Porphycene
KW - Temocene
KW - Vascular targeting
UR - http://www.scopus.com/inward/record.url?scp=84865316737&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000310506400012&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.jconrel.2012.07.025
DO - 10.1016/j.jconrel.2012.07.025
M3 - Article
C2 - 22841794
AN - SCOPUS:84865316737
SN - 0168-3659
VL - 162
SP - 355
EP - 363
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -